2005 Fiscal Year Final Research Report Summary
Development of a combination therapy of cell therapy and deep brain stimulation for Parkinson disease
| Project/Area Number |
16591438
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Nagoya University |
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Principal Investigator |
KAJITA Yasukazu Nagoya University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (70303617)
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| Co-Investigator(Kenkyū-buntansha) |
KANEOKE Yoshiki National Institute for Physiological Sciences, Associate Professor, 自然科学研究機構・生理学研究所, 助教授 (20280589)
NATSUNE Atsushi Nagoya University, University Hospital, Research Associate, 医学部附属病院, 助手 (30362255)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Parkinson diesease / deep brain stimulation / subthalamic nucleus / neuroprotective effect / substantia nigra / rat / single unit recording / dyskinesia |
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| Research Abstract |
The goal of this study is to develop the new neuroprotective therapy for Parkinson disease by a combination of deep brain stimulation and cell therapy. First, we demonstrated that long-term electrical stimulation of subthalamic nucleus (STN) had neuroprotective effect against degeneration of dopaminergic neurons by assessing motor functional and immunohistological findings in hemiparkinsonian rats. In 6-hydroxydopamine (6-OHDA) injected rats, continuous STN stimulation prevented the amphetamine induced abnormal rotation movement. Tyrosine hydroxylase -immunoreactive neurons in the pars compacta of the substantia nigra were significantly preserved in the animals treated by STN stimulation, following the 6-OHDA injections into the striatum. Second, to clarify the neuroprotective mechanism of STN stimulation, we evaluated neurotransmitter including glutamete and γ-amino butyric acid by using micro dialysis following the STN stimulation. However, our data was inconsistent and did not reach the significant findings. Third, we obtained Neural stem cells (NSCs) from fetal human telencephalon of 15-week gestation, and generated the, immortalized NSC cell lines using a retroviral vector encoding v-myc oncogene. To see if intravenously delivered NSCs could migrate to lesioned central nervous system (CNS) and to determine the time course of their migration. The stem cells were labeled by Dil CellTracker ex vivo. Injured nude mice 3,7 or 10 days after the spinal cord compression were injected with the labeled NSCs via tail vein. The grafted cells started to be found at the lesioned spinal cord from 3 days after the compression, and on 3 to 7 days after the compression, larger number of the grafted cells was found by the immunohistochemical method. But almost no grafted cells were found at the lesioned site if NSCs were injected on 10 days after the compression. This study represents the first report of migration of the cell lines of NSCs to the injured CNS.
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